Everolimus (RAD001)MTOR inhibitor CAS# 159351-69-6 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 159351-69-6 | SDF | Download SDF |
| PubChem ID | 23305274 | Appearance | Powder |
| Formula | C53H83NO14 | M.Wt | 958.22 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | RAD001; SDZ-RAD | ||
| Solubility | DMSO : ≥ 54 mg/mL (56.35 mM) H2O : < 0.1 mg/mL (insoluble) *"≥" means soluble, but saturation unknown. | ||
| SMILES | CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)OCCO)C)C)O)OC)C)C)C)OC | ||
| Standard InChIKey | HKVAMNSJSFKALM-CNPAPGRKSA-N | ||
| Standard InChI | InChI=1S/C53H83NO14/c1-32-16-12-11-13-17-33(2)44(63-8)30-40-21-19-38(7)53(62,68-40)50(59)51(60)54-23-15-14-18-41(54)52(61)67-45(35(4)28-39-20-22-43(66-25-24-55)46(29-39)64-9)31-42(56)34(3)27-37(6)48(58)49(65-10)47(57)36(5)26-32/h11-13,16-17,27,32,34-36,38-41,43-46,48-49,55,58,62H,14-15,18-26,28-31H2,1-10H3/b13-11-,16-12+,33-17+,37-27-/t32-,34-,35-,36-,38-,39+,40+,41+,43-,44+,45+,46-,48-,49+,53-/m1/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Everolimus (RAD001) is an inhibitor of mTOR for FKBP12 with IC50 of 1.6-2.4 nM. | |||||
| Targets | mTOR (FKBP12) | |||||
| IC50 | 1.6-2.4 nM | |||||
| Cell experiment: [1] | |
| Cell lines | The pancreatic tumor cell line Panc-1 and the small cell lung cancer cell line ScLc. |
| Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
| Reacting condition | IC50: 50 μg/mL (Panc-1); 5 μg/mL (ScLc), 24h |
| Applications | Everolimus exerted antiproliferation activity. It dose-dependently inhibited BrdU incorporation in Panc-1 and ScLc with IC50 values of 50 μg/mL and 5 μg/mL, respectively. Both are high concentrations that would not be possible in humans. Therapeutic serum levels of everolimus range between 0.005 and 0.01 μg/mL. |
| Animal experiment : [2] | |
| Animal models | TgMISIIR-TAg-DR26 mice model of ovarian cancer |
| Dosage form | RAD001 was formulatedat 2% (w/v) in a microemulsion vehicle and was diluted in double-distilled water just before administration by gavage. Mice were treated with placebo (control) or 5 mg/kg of RAD001 twice weekly started from age of 5 weeks and continued to 20 weeks. Mice treated with placebo or RAD001 were scanned by MRM. |
| Application | RAD001 suppressed tumorigenesis. Body weights of RAD001-treated mice were ~10% lower than in placebo-treated mice. |
| Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
| References: [1] Stracke S, Ramudo L, Keller F, et al. Antiproliferative and overadditive effects of everolimus and mycophenolate mofetil in pancreas and lung cancer cells in vitro. Transplantation proceedings. Elsevier, 2006, 38(3): 766-770. [2] Mabuchi S, Altomare D A, Connolly D C, et al. RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer. Cancer Research, 2007, 67(6): 2408-2413. | |
Everolimus (RAD001) Dilution Calculator
Everolimus (RAD001) Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.0436 mL | 5.218 mL | 10.436 mL | 20.872 mL | 26.09 mL |
| 5 mM | 0.2087 mL | 1.0436 mL | 2.0872 mL | 4.1744 mL | 5.218 mL |
| 10 mM | 0.1044 mL | 0.5218 mL | 1.0436 mL | 2.0872 mL | 2.609 mL |
| 50 mM | 0.0209 mL | 0.1044 mL | 0.2087 mL | 0.4174 mL | 0.5218 mL |
| 100 mM | 0.0104 mL | 0.0522 mL | 0.1044 mL | 0.2087 mL | 0.2609 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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Everolimus, also known as RAD001, is a potent and orally bio-available inhibitor of mammalian target of rapamycin (mTOR), a key component of active PI3K/Akt pathway in human cancers. It binds to intracellular receptor FKBP12 in the mTOR pathway with high affinity forming an everolimus-FKBP12 complex. The complex further binds to mTOR resulting in reducing the activity of the downstream effectors S6 ribsomal protein kinase (S6K1) and translational repressor protein eukaryotic elongation factor 4E-binding protein (4EBP). Besides its immunosuppressive activity for the prevention of organ transplant rejection, everolimus exhibits antineoplastic activity and is currently used to treat renal cell cancer and other tumors.
Reference
G Anandappa, AE Hollingdale, and TG Eisen. Everolimus – a new approach in the treatment of renal cell carcinoma. Cancer Management and Research 2010:2 61-70
Laura Elibenschutz, Delia Colombo, and Caterina Catricala. Everolimus for compassionate use in multiple basal cell carcinomas. Case Reports in Dermatological Medicine 2013
Raffaele Pezzani, Beatrice Rubin, Marco Redaelli, Claudia Radu, Susi Barollo, Maria Verena Cicala, Monica Salva, Caterina Mian, Carla Mucignat-Caretta, Paolo Simioni, Maurizio Iacobone and Franco Mantero. The antiproliferative effects of ouabain and everolimus on adrenocortical tumor cells. Endocrine journal, 2013
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Everolimus (RAD001) sensitizes prostate cancer cells to docetaxel by down-regulation of HIF-1alpha and sphingosine kinase 1.[Pubmed:27821815]
Oncotarget. 2016 Dec 6;7(49):80943-80956.
Resistance to docetaxel is a key problem in current prostate cancer management. Sphingosine kinase 1 (SK1) and phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathways have been implicated in prostate cancer chemoresistance. Here we investigated whether their combined targeting may re-sensitize prostate cancer cells to docetaxel.In hormone-insensitive PC-3 and DU145 prostate cancer cells the mTOR inhibitor Everolimus (RAD001) alone did not lead to significant cell death, however, it strongly sensitized cells to low levels (5 nM) of docetaxel. We show that mTOR inhibition has led to a decrease in hypoxia-inducible factor-1alpha (HIF-1alpha) protein levels and SK1 mRNA. HIF-1alpha accumulation induced by CoCl2 has led to a partial chemoresistance to RAD001/docetaxel combination. SK1 overexpression has completely protected prostate cancer cells from RAD001/docetaxel effects. Using gene knockdown and CoCl2 treatment we showed that SK1 mRNA expression is downstream of HIF-1alpha. In a human xenograft model in nude mice single RAD001 and docetaxel therapies induced 23% and 15% reduction in prostate tumor volume, respectively, while their combination led to a 58% reduction. RAD001 alone or in combination with docetaxel has suppressed intratumoral mTOR and SK1 signaling, however as evidenced by tumor size, it required docetaxel for clinical efficacy. Combination therapy was well tolerated and had similar levels of toxicity to docetaxel alone.Overall, our data demonstrate a new mechanism of docetaxel sensitization in prostate cancer. This provides a mechanistic basis for further clinical application of RAD001/docetaxel combination in prostate cancer therapy.
Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells.[Pubmed:28061438]
Oncotarget. 2017 Feb 14;8(7):11206-11218.
The inhibitor of PI3K-AKT-mTOR pathway, such as Rad001, has not shown therapeutic efficacy as a single agent in prostate cancer. Arsenic trioxide induces the autophagic pathway in prostate cancer cells. We identified Arsenic trioxide can synergize with Rad001 to induce cytotoxicity of prostate cancer cells. Moreover, we identified synergistic induction of autophagy and apoptosis as the underlying mechanism. This enhanced autophagic cell death is accompanied by increased Beclin1 mRNA stability as well as upregulation of ATG5-ATG12 conjugate, Beclin1, and LC3-2. Rad001 and ATO also can synergistically inhibit tumors in prostate cancer xenograft animal model. These results identify and validate a novel mechanism to enhance and expand the existing targeted therapeutic agent to treat prostate cancer.
Everolimus (RAD001) ameliorates vascular cognitive impairment by regulating microglial function via the mTORC1 signaling pathway.[Pubmed:27725116]
J Neuroimmunol. 2016 Oct 15;299:164-171.
Vascular dementia (VaD) is a widely prevalent and devastating disease. Despite the tremendous complexity that limits understanding of the pathophysiology of VaD, microglial dysfunction has been attributed, in part, to immune microenviroment disorder and finally leads to cognitive deficits. Considered the mammalian target of rapamycin complex 1 (mTORC1) is a key player in regulation of glial function, our work focused on whether the mTOR inhibitor Everolimus (RAD001) could overcome the destructive microglial function, change the phenotype and ameliorate cognitive decline induced by chronic cerebral hypoperfusion. Strikingly, the results suggest that inhibition of the mTORC1 activity by RAD001 ameliorates VaD by restoring microglia's M1/M2 balance. Therefore, RAD001 may have promise as a therapy for VaD disease.
